Prior studies in this laboratory have indicated that the biological behavior of human breast cancer reflects an interaction between the intrinsic aggressive potential of the cancer and tumor-retarding responses of the host. The former is correlated with the nuclear grade of the cancer cells while the latter appears to be correlated with cell-mediated immunity (CMI) against the autologous cancer tissue. CMI to autologous breast cancer tissue is typically associated with CMI to the gp55 component of RIII murine mammary tumor virus. We plan to expand the scope of our prior studies in order to more critically characterize the nature of the prognostically significant CMI of the host. CMI to autologous breast tissue will be evaluated by means of a skin window (SW) and a leukocyte migration test (LMT) against precisely characterized lesions, viz. invasive and in situ carcinomas, precancerous mastopathy and normotypic lesions. Simultaneous LMT's will be performed against RIII-gp55. Such testing of clinicopathologically classified breast cancer patients at periodic postoperative intervals will evaluate the prognostic significance of CMI to RIII-gp55 and autologous breast cancer. The possibility that breast cancer immunogen(s) and RIII-gp55 share similar CMI-determinants will be evaluated by means of combined physiochemical and immunological procedures. The proposed studies should advance our understanding of the development and biological behavior of breast cancer and provide a basis for new approaches to immunotherapy and immunoprophylaxis.